Controlling synaptotagmin activity by electrostatic screening.

Controlling synaptotagmin activity by electrostatic screening.
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DOI:
10.1038/nsmb.2375
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发表时间:
2012-10
影响因子:
16.8
通讯作者:
Jahn, Reinhard
Jahn, Reinhard
中科院分区:
生物学1区
文献类型:
--
作者:
Park, Yongsoo;Hernandez, Javier M.;van den Bogaart, Geert;Ahmed, Saheeb;Holt, Matthew;Riedel, Dietmar;Jahn, Reinhard

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Exocytosis of neurosecretory vesicles is mediated bythe SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins syntaxin-1, synaptobrevin, and SNAP-25, with synaptotagmin functioning as the major Ca2+-sensor for triggering membrane fusion. Here we show that bovine chromaffin granules readily fuse with large unilamellar liposomes in a SNARE-dependent manner. Fusion is enhanced by Ca2+ but only if the target liposomes contain PI(4,5)P2 and if polyphosphate anions such as nucleotides or pyrophosphate are present. Ca2+-dependent enhancement is mediated by endogenous synaptotagmin-1. Polyphosphates operate by an electrostatic mechanism that reverses an inactivating cis-association of synaptotagmin-1 with its own membrane whereas trans-binding is not affected. Hence, balancing trans- and cis-membrane interactions of synaptotagmin may be a crucial element in the pathway of Ca2+-dependent exocytosis.
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